Infectious viruses, unless inactivated, can be readily transmitted from biological products derived from human plasma as well as recombinant-DNA and monoclonal antibody sources. The hepatitis B virus (HBV) as well as the agents of non-A and non-B hepatitis (NANBHV) have plagued patients, physicians and manufacturers for many years. In recent years, the human immunodeficiency virus (HIV)--the etiologic agent of acquired immunodeficiency syndrome (AIDS)--has become a very serious and epidemic problem. In several instances, coagulation factor concentrates have transmitted HIV to hemophiliacs, some of whom have subsequently developed AIDS (an estimated 65% of the 20,000 hemophiliacs in the United States are infected with HIV, Wall Street Journal, Dec. 27, 1990. Morgenthaler, a leading researcher in this field, states in his preface to Viral Inactivation in Plasma Products (1989) that: "Clearly, there is a need for methods that inactivate viruses in blood, without causing harm to the components intended for therapeutic use."
Viral inactivation of recombinant-DNA products is still a major and active concern for the biotechnology and pharmaceutical industries as well as the regulatory agencies. The FDA in Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use states that: "It is strongly recommended that validated procedures . . . which remove and/or inactivate viruses and DNA if present be employed during purification. . . ." For reasons of safety and public health, the quest is to discover and develop processes for inactivating viruses without denaturing the biologically active products which are commonly labile and quite sensitive to conventional viral inactivation techniques.
There exists substantial difficulty in inactivating viruses in the presence of thermally labile and sensitive proteins without utilizing additives which may be carcinogenic, toxic and/or damaging to biologically active compounds. These additives, which must be removed in a sterile post-process step, place an additional cost and time burden on conventional viral inactivation techniques.
Embodiments of this invention provide novel methods and apparatus for inactivating viruses, especially enveloped or lipid-coated viruses, and nonenveloped, protein encased viruses in proteinaceous products without incurring substantial denaturation.